Novel SLC16A2 Frameshift Mutation as a Cause of Allan-Herndon-Dudley Syndrome and its Implications for Carrier Screening.

Background: Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked neurodevelopmental disorder caused by mutations in the solute carrier family 16-member 2 (SLC16A2) gene. This syndrome leads to significant psychomotor disabilities, thyroid dysfunction, and abnormal brain development. This case report describes the genetic cause of AHDS in a male proband and to expanding the mutation spectrum of the SLC16A2 gene.

Methods: A blood specimen was collected from a one-year-old child with delayed development and abnormal thyroid function and this was followed by whole-exome sequencing (WES) was performed on the proband to identify potential genetic mutations. Sanger sequencing was subsequently used to confirm the findings and determine the inheritance pattern of the mutation within the family.

Results: The proband, who presented with developmental delay, thyroid dysfunction, and abnormal brain development, was found to have a novel hemizygous frameshift mutation, c.513_538del (p.Ile172Cysfs*60), in the SLC16A2 gene (NM_006517.5). This mutation was inherited from his asymptomatic mother, confirming the X-linked inheritance pattern. The mutation is classified as likely pathogenic, contributing to the clinical presentation observed in the proband.

Conclusion: This study identified a novel frameshift mutation in the SLC16A2 gene associated with AHDS, thereby expanding the known mutation spectrum of this gene. Given the significant impact of AHDS on neural development and hormone secretion, it is recommended that this gene be included in carrier screening panels in China, particularly for families with a history of related neurodevelopmental disorders.